Childhood Langerhans cell histiocytosis with severe lung involvement: a nationwide cohort study
Solenne Le Louet, Mohamed-Aziz Barkaoui, Jean Miron, Claire Galambrun, Nathalie Aladjidi, Pascal Chastagner, Kamila Kébaïli, Corinne Armari‐Alla, Anne Lambilliotte, Julien Lejeune, Despina Moshous, Valéria Della Valle, Chiara Siléo, Hubert Ducou Le Pointe, Jean‐François Chateil, Sylvain Renolleau, Jean‐Eudes Piloquet, Aurélie Portefaix, Ralph Epaud, R. Chiron, Emmanuelle Bugnet, Gwenaël Lorillon, A. Tazi, Jean-François Emile, Jean Donadieu, Sébastien Héritier
Abstract
BACKGROUND: Lung involvement in childhood Langerhans cell histiocytosis (LCH) is infrequent and rarely life threatening, but occasionally, severe presentations are observed. METHODS: Among 1482 children (< 15 years) registered in the French LCH registry (1994-2018), 111 (7.4%) had lung involvement. This retrospective study included data for 17 (1.1%) patients that required one or more intensive care unit (ICU) admissions for respiratory failure. RESULTS: The median age was 1.3 years at the first ICU hospitalization. Of the 17 patients, 14 presented with lung involvement at the LCH diagnosis, and 7 patients (41%) had concomitant involvement of risk-organ (hematologic, spleen, or liver). Thirty-five ICU hospitalizations were analysed. Among these, 22 (63%) were secondary to a pneumothorax, 5 (14%) were associated with important cystic lesions without pneumothorax, and 8 (23%) included a diffuse micronodular lung infiltration in the context of multisystem disease. First-line vinblastine-corticosteroid combination therapy was administered to 16 patients; 12 patients required a second-line therapy (cladribine: n = 7; etoposide-aracytine: n = 3; targeted therapy n = 2). A total of 6 children (35%) died (repeated pneumothorax: n = 3; diffuse micronodular lung infiltration in the context of multisystem disease: n = 2; following lung transplantation: n = 1). For survivors, the median follow-up after ICU was 11.2 years. Among these, 9 patients remain asymptomatic despite abnormal chest imaging. CONCLUSIONS: Severe lung involvement is unusual in childhood LCH, but it is associated with high mortality. Treatment guidelines should be improved for this group of patients: viral infection prophylaxis and early administration of a new LCH therapy, such as targeted therapy.